What is GHK‑Cu (glycyl‑L‑histidyl‑L‑lysine bound to copper)?

What is GHK-Cu?

GHK-Cu (glycyl-L-histidyl-L-lysine bound to copper) is a naturally occurring tripeptide-copper complex found in human plasma, saliva, and urine that functions primarily as a tissue regeneration and wound healing agent, with plasma levels declining from approximately 200 ng/mL at age 20 to 80 ng/mL by age 60. 1, 2

Chemical Structure and Binding Properties

• GHK is a tripeptide composed of three amino acids: glycine, histidine, and lysine 1
• The peptide has very high affinity for copper(II) ions and readily forms the copper complex GHK-Cu 3, 2
• The copper binding occurs through the nitrogen atoms in the peptide structure, creating a stable planar ring complex 3

Biological Functions and Mechanisms

Wound Healing and Tissue Repair

• GHK-Cu accelerates wound healing in skin, hair follicles, gastrointestinal tract, boney tissue, and induces systemic wound healing in animal models 1
• The complex stimulates both synthesis and breakdown of collagen and glycosaminoglycans, modulating the activity of metalloproteinases and their inhibitors 1
• It specifically increases type I and type III collagen synthesis, with stimulation of collagen synthesis being twice that of non-collagen proteins 4
• GHK-Cu promotes accumulation of dermatan sulfate, chondroitin sulfate, and the small proteoglycan decorin 1, 4

Cellular Effects

• The peptide attracts immune and endothelial cells to injury sites 1
• It restores replicative vitality to fibroblasts after radiation therapy 1
• Stimulation of collagen synthesis begins at concentrations between 10⁻¹² and 10⁻¹¹ M, with maximal effect at 10⁻⁹ M 5

Gene Regulation

• GHK is capable of up- and downregulating at least 4,000 human genes, essentially resetting DNA to a healthier state 1
• It modulates genes critical for neuronal development and maintenance 3
• The peptide targets anti-inflammatory and epigenetic pathways 2

Clinical and Cosmetic Applications

Dermatologic Uses

• In cosmetic products, GHK-Cu tightens loose skin and improves elasticity, skin density, and firmness 1
• It reduces fine lines, wrinkles, photodamage, and hyperpigmentation 1
• The complex increases keratinocyte proliferation 1

Therapeutic Potential

• GHK-Cu possesses antioxidant and anti-inflammatory properties demonstrated in vitro and in vivo 2
• It has been proposed as a therapeutic agent for skin inflammation, chronic obstructive pulmonary disease, and metastatic colon cancer 1
• Preliminary observations suggest potential for reversing cognitive impairment in aging through anti-inflammatory and epigenetic mechanisms 3, 2

Important Clinical Context

Relationship to Copper Metabolism

• While GHK-Cu contains copper, it functions as a distinct biological entity separate from standard copper supplementation 1, 3
• The copper in GHK-Cu is tightly bound in a specific chelate complex that determines its biological activity 2
• This is fundamentally different from the free copper or ceruloplasmin-bound copper discussed in nutritional copper guidelines 6

Safety Profile

• GHK has a long history of safe use in wound healing and anti-aging skin care 3
• The peptide was originally discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue 3

Key Distinction from Nutritional Copper

GHK-Cu should not be confused with copper supplementation for nutritional deficiency. The tripeptide-copper complex functions through specific receptor-mediated mechanisms and gene regulation pathways that are distinct from the role of copper as an essential trace element in copper-dependent enzymes like lysyl oxidase, ceruloplasmin, and cytochrome c oxidase 1, 3 versus 6.